Neoadjuvant chemoradiotherapy for resectable esophageal cancer:an in-depth study of randomized controlled trials and literature review

Surgery following neoadjuvant chemoradiotherapy(NCRT) is a common multidisciplinary treatment for resectable esophageal cancer(EC). After analyzing 12 randomized controlled trials(RCTs), we discuss the key issues of surgery in the management of resectable EC. Along with chemoradiotherapy, NCRT is recommended for patients with squamous cell carcinoma(SCC) and adenocarcinoma(AC), and most chemotherapy regimens are based on cisplatin, fluorouracil(FU), or both(CF). However, taxane-based schedules or additional studies, together with newer chemotherapies, are warranted. In nine clinical trials, post-operative complications were similar without significant differences between two treatment groups. In-hospital mortality was significantly different in only 1 out of 10 trials. Half of the randomized trials that compare NCRT with surgery in EC demonstrate an increase in overall survival or disease-free survival. NCRT offers a great opportunity for margin negative resection, decreased disease stage, and improved loco-regional control. However, NCRT does not affect the quality of life when combined with esophagectomy. Future trials should focus on the identification of optimum regimens and selection of patients who are most likely to benefit from specific treatment options.

Prognostic significance of preoperative and postoperative CK19 and CEA m RNA levels in peripheral blood of patients with gastric cardia cancer

AIM To evaluate the clinical and prognostic significance of preoperative and postoperative cytokeratin 19(CK19) and carcinoembryonic antigen(CEA) m RNA levels in peripheral blood of patients with gastric cardia cancer(GCC).METHODS We detected the preoperative and postoperative mR NA levels of CK19 and CEA in peripheral blood of 129 GCC patients by using reverse transcription-polymerase chain reaction and evaluated their clinical and prognostic significance by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard analysis. A new prognostic model which stratified patients into three different risk groups was established based on the independent prognostic factors.RESULTS Elevated preoperative and postoperative CK19 and CEA mR NA levels in peripheral blood of GCC patients were associated with lymph node metastasis. Univariate analysis showed that tumor size, histological grade, depth of tumor invasion, lymph node metastasis, preoperative CK19 m RNA, and preoperative and postoperative CEA m RNA levels were correlated with the prognosis of GCC patients. The multivariate analysis showed that lymph node status(P = 0.018), preoperative CK19(P = 0.035) and CEA(P = 0.011) m RNA levels were independent prognostic factors for overall survival(OS). The 5-year OS rates for the low-, intermediate-, and high-risk groups were 48.3%, 22.6%, and 4.6%, respectively(P < 0.001).CONCLUSION Elevated preoperative CK19 and CEA mR NA levels may be regarded as promising biomarkers for predicting lymph node metastasis and poor prognosis in patients with GCC. This new prognostic model may help us identify the subpopulations of GCC patients with the highest risk.

The biological role of the CXCL12/CXCR4 axis in esophageal squamous cell carcinoma

Esophageal cancer is the eighth most common malignant tumor and the sixth leading cause of cancer-related death worldwide.Esophageal squamous cell carcinoma(ESCC)is the main histological type of esophageal cancer,and accounts for 90%of all cancer cases.Despite the progress made in surgery,chemotherapy,and radiotherapy,the mortality rate from esophageal cancer remains high,and the overall 5-year survival rate is less than 20%,even in developed countries.The C-X-C motif chemokine ligand 12(CXCL12)is a member of the CXC chemokine subgroup,which is widely expressed in a variety of tissues and cells.CXCL12 participates in the regulation of many physiological and pathological processes by binding to its specific receptor,C-X-C motif chemokine receptor type 4(CXCR4),where it causes embryonic development,immune response,and angiogenesis.In addition,increasing evidence indicates that the CXCL12/CXCR4 axis plays an important role in the biological processes of tumor cells.Studies have shown that CXCL12 and its receptor,CXCR4,are highly expressed in ESCC.This abnormal expression contributes to tumor proliferation,lymph node and distant metastases,and worsening prognosis.At present,antagonists and imaging agents against CXCL12 or CXCR4 have been developed to interfere with the malignant process and monitor metastasis of tumors.This article summarizes the structure,function,and regulatory mechanism of CXCL12/CXCR4 and its role in the malignancy of ESCC.Current results from preclinical research targeting CXCL12/CXCR4 are also summarized to provide a reference for the clinical diagnosis and treatment of ESCC.

Elevated serum levels of human relaxin-2 in patients with esophageal squamous cell carcinoma

AIM: To assess the prognostic value of serum human relaxin 2 (H2 RLN) level in patients with esophageal squamous cell carcinoma (ESCC). METHODS: From October 1998 to September 2009, 146 patients with histopathologically confirmed ESCC were enrolled in this study. One hundred patients underwent en bloc esophagectomy, and 46 patients with unresectable tumors underwent palliative surgery. Five of the 146 patients died of surgical complications. Serum levels of H2 RLN were measured by enzyme linked immunosorbent assay. The relationship between serum H2 RLN level and each of the clinicopathological parameters was analyzed using the χ2 test. Patients were classified into two groups according to their H2 RLN level (< 0.462 ng/mL vs ≥ 0.462 ng/mL). When any analysis cell had fewer than five cases, the Fisher's exact test was used. The statistical difference between groups A and B in each clinicopathological category was determined by the Student's t test (two-tailed) or analysis of variance. Survival curves were plotted using the Kaplan-Meier method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: ESCC patients tended to have significantly higher serum H2 RLN concentrations (0.48 ± 0.17 ng/ mL, n=141) compared with the healthy control group (0.342 ± 0.12 ng/mL, n=112). There was a significant difference between patients with lymph node involvement (0.74 ± 0.15 ng/mL, n=90), distant metastasis (0.90 ± 0.19 ng/mL, n=32) and those without lymph node involvement (0.45 ± 0.12 ng/mL, n=51), and distant metastasis (0.43 ± 0.14 ng/mL, n=109), respectively (P < 0.01). Patients with high H2 RLN levels (≥ 0.462 ng/mL) had a poorer prognosis than patients with low serum H2 RLN levels (< 0.462 ng/mL; P=0.0056). The H2 RLN level was also correlated with survival and tumor-node-metastasis staging, but not with age, tumor size, gender, lymphovascular invasion or the histological grade of tumors. Cox regression analysis showed that H2 RLN was an independent variable. CONCLUSION: Serum concentrations of H2 RLN are frequently elevated in ESCC patients and are correlated with disease metastasis and survival. Serum concentrations of H2 RLN may be an important prognostic marker in ESCC patients.

The extent and value of lymphadenectomy in the surgical treatment of gastroesophageal junction carcinoma

我们学习了的目的在胃的食道的连接(GEJ ) 的癌的外科的治疗的淋巴腺切除术的程度和价值。经历了外科的切除术的有 GEJ 的 217 个病人回顾地被分析的方法。淋巴腺切除术的程度被划分成 5 种类型(到 D4 的 D0 ) ，操作的治愈可能性作为 A， B 和 C 被分级。结果病人如下被对待：186 与近似 gastrectomy， 31 与全部的 gastrectomy， 97 与联合内脏的切除术。经历了 D1， D2 和 D3 淋巴腺切除术的病人是分别地 158， 58 和 1。与等级 A， B 和 C 的切除术被执行的病人分别地是 53， 107 和 57。所有病人与淋巴腺切除术被执行并且很好登记了。淋巴节点转移发生在 157 种情况(72.4%) 中。在 1， 2， 3， 4， 7， 9， 12 和 110 象在肺的系带一样组织的组的淋巴节点转移率比另外的组高。2868 个淋巴节点被移开，在哪个(22.8%) 655 表明了转移的存在。在这些的变形的度组织的全部的淋巴节点与另外的组相比是更高的。结论在 D1 淋巴腺切除术和 D2 的幸存率为所有病人是类似的，并且可以在 stage-IIIb 病人在第二 and 有一些差别为 D1 淋巴腺切除术和 D2 的第三年。在阶段 IIIb 的 D2 淋巴腺切除术的幸存率比 D1 和 D2 淋巴腺切除术的比在 stage-IV 病人的 D1 优异好。等级 A 和 B 操作的幸存率比等级 C，和幸存等级 A 评价是好一些的也比 B 高。

HIF-1α siRNA Leads to Apoptosis of Pancreatic Cancer Cells under Hypoxic Conditions

OBJECTIVE To explore the role of hypoxic inducible factor-1α(HIF-1α) in the proliferation and apoptosis of pancreatic cancercells under hypoxic conditions.METHODS A cassette encoding small interference RNA (siRNA)targeting HIF-1α mediated by recombinant adeno-associated virus(rAAV) was constructed, giving rAAV-siHIF. rAAV-siHIF or rAAV-hrGFP was transfected into exponentially growing MiaPaCa2cells under hypoxic conditions. Then, the expression of HIF-1αmRNA and protein, the proliferation and apoptosis of MiaPaCa2cells were examined, using real-time PCR, Western Blot, MTT andTUNEL, respectively.RESULTS Under hypoxic conditions, rAAV-siHIF inhibited theexpression of HIF-1α mRNA and protein in MiaPaCa2 cells. At thesame time, rAAV-siHIF decreased MiaPaCa2 cell proliferation andinduced apoptosis. However, rAAV-hrGFP had no effect on theexpression of HIF-1α as well as the proliferation and apoptosis ofMiaPaCa2 cells under hypoxic conditions.CONCLUSION Under hypoxic conditions, HIF-1α plays a keyrole in the proliferation of MiaPaCa2 cells, and inhibition of HIF-1α expression can lead to MiaPaCa2 cell apoptosis.

Study of the Value of Combined Multiorgan Resection in Surgical Treatment of Carcinoma of the Gastric Cardia

OBJECTIVE:To determine the value of resection of combined visceral organs in surgical treatment of gastric cardiac carcinoma. METHODS:We retrospectively analyzed 217 random patients with car- cinoma of the gastric cardia who underwent a gastric cardiac resection.The patients had been treated as fol ows:186 with partial gastrectomy,31 with total gastrectomy,97 with a combined-visceral resection,of which 82 under- went a splenectomy plus partial pancreatectomy,10 with splenectomy alone and 5 with partial hepatectomy and diaphragmatectomy. RESULTS:The total patients were divided into 3 groups:128 with a gas- trectomy alone,10 with gastrectomy and splenectomy,and 82 with gastrec- tomy and splenectomy plus pancreatectomy.The operating times for these 3 groups were respectively 3.0 h,3.1 h and 3.8 h.The hospitalization times were respectively 23.8 d,31.2 d and 25.9 d.No differences in post-operative complications were found between these 3 groups.There were 92 patients who underwent a gastrectomy combined with a splenectomy and(or)the pancreatectomy,in which 92 No.10 lymph nodes were eliminated,with an average of one in each patient.Among the 125 patients not receiving a sple- nectomy but with elimination of lymph nodes,82 underwent a gastrectomy combined with partial pancreatectomy,of which 107 lymph nodes were elimi- nated for the No.11 group,with an average of 1.3 in each patient.There was a statisticaly significant difference between the 2 groups.The overal survival rates were similar in the 3 groups showing no statistical differences, but was higher in the Stage III patients with a combined resection of multi- organs.For patients in the Stage IV without resection of multi-organs,the survival rate was higher,but there was no significant difference between the 2 groups. CONCLUSION:It is difficult to determine precisely the involvement of para-tumorous organs with the eye during an operation.Combining a sple- nectomy with a pancreatectomy does not increase the post-operative compli- cations following surgical treatment for carcinoma of the gastric cardia.The combination of a splenectomy and partial pancreatectomy results in a higher survival rate and has an important significance for eliminating the lymph nodes of group 10 and 11,especially for patients in Stage III.In the applica- tion of a resection combining multi-organs,the doctor should make every effort to decrease the trauma and the complications based on the condition that the cancerous tissue is totally resected.

Splenectomy for splenic metastases from malignant adrenal pheochromocytoma: a case report

Splenic metastasis is generally not a common clinical event. However, metastasis to the spleen from adrenal pheochromocytoma is extremely rare and has not been reported in literature. This report presents a case of a 58 year-old male patient who developed spleen-only metastases in July 2007. The patient had a previous history of left epinephroectomy for adrenal pheochromocytoma in January 2003. Abdominal computed tomography demonstrated multiple enhancing lesions suggestive of metastases; thus splenectomy was performed. Pathological examinations confirmed the diagnosis of splenic metastases from pheochromocytoma. The patient was alive without recurrence 48 months after splenectomy. This study is the first report on splenic metastasis from previous adrenal pheochromocytoma, and long-term survival was achieved by splenectomy. A history of malignancy indicates a high index of suspicion for splenic metastasis, and long-term survival can be achieved by splenectomy for spleen-only metastasis.